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Structural basis for the constitutive activity of the melanocortin receptor family

文献类型：期刊论文

作者Feng, Wenbo5; Zhou, Qingtong4,5; Zheng, Chang3; Yang, Dehua3; Wang, Ming-Wei1,2,4,5
刊名STRUCTURE
出版日期2025-06-05
卷号33期号:6页码:20
ISSN号0969-2126
DOI10.1016/j.str.2025.03.004
通讯作者Wang, Ming-Wei(mwwang@simm.ac.cn)
英文摘要The constitutive activity of melanocortin receptors (MCRs) is integral to several physiological processes. The unliganded cryo-electron microscopy structures of MC1R, MC2R, MC3R, MC4R, and MC5R in complex with Gs proteins determined at global resolutions of 2.98 A & ring;, 3.01 A & ring;, 2.75 A & ring;, 3.12 A & ring;, and 2.86 A & ring;, respectively, revealed that their binding poses and interactions with Gs are similar to those of agonist-bound MCRs. The extracellular regions of the transmembrane helices (TMs) exhibit distinct conformational rearrangements, characterized by varying shifts of TM3 and outward displacements of TM4. These variations represent unique structural features of constitutively activated MCRs. Unassigned electron densities were observed within the orthosteric pockets where extensive interactions with cognate ligands occur. In addition, zinc ions, but not calcium, positively regulated MC4R activity in a dose-dependent manner. Our findings provide valuable insights into the molecular mechanisms underlying MCR basal activity and highlight the role of divalent ions in receptor activation.
WOS关键词PROTEIN ; ACTIVATION ; MECHANISM ; SYSTEM ; DOMAIN ; MODEL ; ZN2+
资助项目National Natural Science Foundation of China[82273961] ; National Natural Science Foundation of China[82073904] ; National Natural Science Foundation of China[81872915] ; STI2030-Major Project[2021ZD0203400] ; Hainan Provincial Major Science and Technology Project[ZDKJ2021028]
WOS研究方向Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
语种英语
WOS记录号WOS:001510101700002
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/318407]  
专题中国科学院上海药物研究所
通讯作者Wang, Ming-Wei
作者单位1.Hainan Med Univ, Engn Res Ctr Trop Med Innovat & Transformat, Sch Pharm, Minist Educ, Haikou 570228, Hainan, Peoples R China
2.Res Ctr Deepsea Bioresources, Sanya 572025, Peoples R China
3.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
4.Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai 200032, Peoples R China
5.Shanghai Jiao Tong Univ, Natl Res Ctr Translat Med Shanghai, Res Ctr Med Struct Biol, Ruijin Hosp,Sch Med,State Key Lab Med Genom, Shanghai 200025, Peoples R China
推荐引用方式
GB/T 7714		 Feng, Wenbo,Zhou, Qingtong,Zheng, Chang,et al. Structural basis for the constitutive activity of the melanocortin receptor family[J]. STRUCTURE,2025,33(6):20.
APA Feng, Wenbo,Zhou, Qingtong,Zheng, Chang,Yang, Dehua,&Wang, Ming-Wei.(2025).Structural basis for the constitutive activity of the melanocortin receptor family.STRUCTURE,33(6),20.
MLA Feng, Wenbo,et al."Structural basis for the constitutive activity of the melanocortin receptor family".STRUCTURE 33.6(2025):20.

入库方式： OAI收割

来源：上海药物研究所

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